Outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: validation, comparison and improvement of 2022 ELN genetic risk system

The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and 224 (37.33%) patients in ELN-2022 favorable-, intermediate-, and adverse-risk group respectively and 86 patients (14.33%) experienced a shift in risk stratification compared to ELN-2017. Median and maximum follow-up time were 2.89 (95% CI 2.67 to 3.03) years and 8.78 years. The median overall survival (OS) was 73.8% (95% CI 67.5% to 80.3%), 63.9% (95% CI 56.7% to 72.0%) and 57.6% (95% CI 50.4% to 65.9%) in ELN-2022 favorable-, intermediate-, and adverse-risk group (P < 0.001). OS shortened significantly as the ELN-2022 risk stratification increased but didn’t significantly in ELN-2017 intermediate-risk compared to favorable-risk. Both ELN-2022 and ELN-2017 adverse-risk were associated with increased cumulative incidence of relapse (CIR). Time-dependent receiver operating characteristic (ROC) analysis showed that both ELN-2017 and ELN-2022 risk systems had limited prognostic ability for OS. We modified ELN-2022 risk system with pre-transplant minimal residual disease (MRD) and the modified risk system performed a significantly superior efficacy to ELN-2022 system. Supplementary Information The online version contains supplementary material available at 10.1186/s40164-024-00487-6.

transplantation (allo-HSCT) remains uncertain.Our study aims to shed light on this.
Patients and transplant-related characteristics were listed in Additional file 1: Table S2.Compared to favorable-and intermediate-risk groups, adverse-risk group had a lower percentage of bone-marrow blasts at initial diagnosis (P = 0.036) and a higher proportion of refractory/relapse-and secondary-AML (P = 0.006, p < 0.001, respectively, Additional file 1: Fig. S1).
The three-year and five-year overall survival (OS), event-free survival, cumulative incidence of relapse (CIR) and non-relapse mortality stratified by ELN-2022 and ELN-2017 are shown in Additional file 1: Table S3.Compared to favorable-risk, OS shortened significantly as the ELN-2022 risk stratification increased but didn't significantly in ELN-2017 intermediate-risk (Fig. 1E, F).Pairwise comparisons for OS revealed significant differences between the ELN-2022 favorable-and intermediate-risk groups (P = 0.047) but not between the intermediate-and adverse-risk groups (P = 0.455).Based on ELN-2017 risk stratification, OS was not significantly different between intermediate-and favorable-risk groups (P = 0.115) or between intermediate-and adverse-risk groups (P = 0.115).Both ELN-2022 and ELN-2017 adverserisk were associated with increased CIR. (Fig. 1G, H) Smoothed hazard estimates showed a higher mortality risk within 6 months post-transplantation in ELN-2022 intermediate-risk group than in adverse-risk group.Assessment based on ELN-2017 recommendations indicated that adverse-risk group had the highest hazard ratio for death in 1-year post-transplantation, followed by intermediate-and favorable-risk groups (Additional file 1: Fig. S2).
We performed time-dependent receiver operating characteristic (ROC) analysis to validate the prognostic efficacy of ELN-2022 and ELN-2017 risk systems in our transplant cohort.The AUC for predicting OS gradually increased from one to five years post-transplantation, with the AUC for ELN-2022 consistently higher than of ELN-2017 (Fig. 2A).However, AUC for 3-year and 5-year OS between two ELN versions was not significantly different (P = 0.458, P = 0.838, respectively).
In conclusion, ELN-2022 risk system had superior separation for survival of favorable-and unfavorable-risk groups but poor separate for intermediate-and adverserisk groups.ELN-2017 risk system primarily separates survival of favorable-and adverse-risk groups.Both ELN-2022 and ELN-2017 systems exhibited limited

Fig. 1
Fig. 1 Patients and genetic characteristics and impact of ELN-2022 and ELN-2017 risk stratification on clinical outcomes.A Relationship of risk groups between ELN-2022 and ELN-2017 risk groups; B Distribution of re-stratification in ELN-2017 risk groups.C Landscape of genetic abnormalities defined by ELN-2022 genetic risk categories.The color scale is representative of a number of patients.D Additional mutations stratified by ELN-2022 genetic risk categories.Genes mutated in more than ten patients are shown.E Overall survival stratified by ELN-2022 risk categories.F Overall survival stratified by ELN-2017 risk categories.G Cumulative incidence of relapse stratified by ELN-2022 risk categories.H Cumulative incidence of relapse stratified by ELN-2017 risk categories (See figure on next page.)